The
conversion of alcohols to esters is an important synthetic transformation that
has received considerable attention. Conversion of an alcohol to the
corresponding acetate is typically carried out using acetic anhydride or acetyl
chloride in the presence of pyridine or triethylamine as a catalyst. 4-(Dimethylamino)pyridine (DMAP) is known to cause a
remarkable rate acceleration in this reaction. One problem with tertiary amines is that
they are corrosive, toxic, and often highly unpleasant to work with. Lewis acids have also been reported to
catalyze the acetylation of alcohols.
These include Bi(OTf)3, Sc(OTf)3,,
CoCl2, and I2. Many of these catalysts are either
corrosive (such as I2) or very expensive (scandium salts). With increasing environmental concerns,
it is imperative that new "environmentally friendly" reagents be
developed. Our continued interest in developing environmentally
friendly synthetic methodology prompted us to investigate a mild and catalytic
method for the acylation of alcohols, phenols, and diols utilizing inexpensive,
commercially available reagents.
Herein we wish to report that iron(III) tosylate is a mild catalyst for
the acylation of a variety of alcohols, phenols, and diols (Table 1). As can be seen from Table 1, the
reaction worked well with 1° and 2° alcohols (entries 1-11), and phenols
(entries 15, 16, 17 and 20). When
acetic anhydride was used as the acylating agent the reaction could be carried
out under solvent-free conditions.
With allylic alcohols (entries 3 and 5), the use of solvent (CH3CN)
gave fewer side products. In most
cases, the crude product was found to be ³ 98% pure by 1H and 13C
NMR spectroscopy and further purification was deemed unnecessary. For solubility reasons, CH2Cl2
was used as a solvent in case of benzil (entry
11). Although the methodology was
not broadly applicable to tertiary alcohols, we were able to successfully
acetylate some 3° alcohols. For
example, 1-ethynylcyclohexanol (entry 12) gave a moderate yield of the
corresponding acetate. When
1-methylcyclohexanol (entry 13) was subjected to the reaction conditions (in CH3CN),
the crude product although colored was found to contain mostly (80%) the 3°
acetate. However, chromatography
yielded the pure acetate in only a low yield (38%).

bAll reactions were run at room temperature
unless otherwise mentioned, and reaction progress was monitored by GC or TLC.

cRefers to yield of isolated product that was deemed to be sufficiently
pure (> 98%) by 1H & 13C NMR spectroscopy, unless
otherwise mentioned. All products
have been previously reported in the literature or are commercially
available. The superscript next to
yield refers to literature reference for spectral data of the product.

dReaction was carried out using 5.0 mol % catalyst.

eYield of product after purification by flash chromatography.

fProduct was determined to be 96% pure by
GC

gReaction was carried out using 0.5 mol % catalyst.

hNo
reaction was observed even when the mixture was heated at reflux for 29 h.

iReaction was carried out with 2.6 equivalents of acetic anhydride.

jProduct is commercially available
(CAS # 6963-44-6).

Any
1-methylcyclohexene that may have formed is likely to have been lost during
removal of the solvent on a rotary evaporator, and hence was not seen in the 1H
spectrum of the crude product. The
hindered 3° alcohol, triphenylmethanol (entry 14),
failed to yield the acetate even under reflux conditions, and the starting
material was recovered unchanged.
When
2-phenyl-2-propanol 1 (scheme 1) was subjected to the
reaction conditions, none of the corresponding acetate was isolated. GC analysis of the crude product, which
was obtained as a dark red-brown liquid showed that it mostly (88%) contained
product 3. However, product 3 was isolated only in 26% yield after chromatographic purification
of the crude product. Its identity
was confirmed by 1H and 13C NMR spectroscopy, and HRMS. Based on the fact that the same product
was obtained in the absence of acetic anhydride but at a much slower rate, we
propose that product 3 arises via
the initially formed acetate 2,
which subsequently eliminates and dimerizes via a 3°
carbocation.

Scheme
1

Attempts to make the monoacetate from a symmetrical diol
1, 5-pentanediol (entry 21) using one equivalent of acetic anhydride were not
successful. When 1,5-pentanediol
was reacted with 1.05 equivalents on acetic anhydride, the product was a mixture
of the monocetate, diacetate
and unreacted starting material.
However, formation of the diacetate proceeded
smoothly in the presence of 2.6 equivalents of acetic anhydride. We have previously reported that
aliphatic TBDMS groups can be cleaved with iron(III) tosylate in the presence
of a phenolic TBDMS ether. Consistent with this observation is the fact that we
were able to acetylate a phenol in the presence of a phenolic TBDMS group
(entry 17).